Application of Carbomer in Ophthalmic Gel Preparation
1. Ocular Drug Delivery System
Due to the special eye protection mechanism, such as tear flushing, blinking movement, corneal low permeability and many other physiological factors, ordinary eye drops will be quickly eliminated, drug absorption is limited, and the bioavailability after eye administration is restricted. Improving the bioavailability of drugs in ophthalmic preparations mainly depends on the retention time of drugs in the eye (cornea). The longer the time, the greater the amount of drugs absorbed and the better the curative effect. Some dosage forms such as suspension or eye ointment can stay in the eyes, but solid or semi-solid will make the patient uncomfortable. Carbomer gel has good adhesion, non-toxic and non irritant. It can extend the time of action and increase the absorption and utilization of drugs. The study showed that the contact time between Carbomer gel and eye was concentration dependent.
2. Characteristics of Carbomer Gel
Carbomer solution can form a uniform, transparent and stable hydrogel at ph6-12. It has the characteristics of water-soluble matrix, fast release, no greasy, easy to coat, easy to clean, no irritation to skin and mucosa, comfortable feeling after use, can be mixed with aqueous solution, and can absorb tissue exudate, which is good for removing the secretion, and is widely used in ophthalmic gel preparations.
3. Carbomer Ophthalmic Preparations
3.1. Pilocarpine Gel
A comparative study of pilocarpine eyedrops and gels for glaucoma was carried out abroad. It was found that the sustained release effect of gel preparation was better than that of pure liquid preparations or other solutions with a certain viscosity. Moreover, the sustained release effect of 4% Carbomer -940 gel was the best. At present, domestic pilocarpine gel has been put on the market and used in clinic.
3.2. Atropine Gel
Atropine eye ointment can regulate paralysis, optometry, mydriasis, treatment of ametropia and acute irirtis in ophthalmic treatment. In the past, the matrix materials of eye ointment were mainly vaseline and lanolin. Its disadvantages are greasy, difficult to apply, strong irritation, blurred vision after medication, difficult to master the dose and so on. The water soluble gel matrix based on Carbomer is easy to be smeared, non irritant and easy to control. It is easy to be accepted by patients.
3.3. Left Ofloxacin Gel
Levofloxacin is antibacterial by inhibiting the synthesis of dna. Its antibacterial activity is 2 times that of ofloxacin. It is currently recognized as an effective ophthalmic antibiotic. It has the advantages of wide antibacterial spectrum, high efficiency, low toxicity and stability. It has been used to treat keratitis, conjunctivitis, corneal ulcer, blepharitis, wheat granuloma and dacryocystitis. Based on the physiological characteristics of the eyes, carbofur is used as thickening agent to prepare levofloxacin ophthalmic gel. The most outstanding feature of the gel is its strong adhesion and high surface activity, which can increase the contact time and area of drugs and eyes, reduce the frequency of medication, enhance the efficacy of drugs, reduce the irritation of the eyes, and improve the transparency, and not affect the sight. At the same time, the logistics entrance of medicine is reduced. Discomfort caused by nose.
3.4. Carbomer Eye Drops
Carbomer eye drops is produced by germany, containing 0.2% Carbomer hydrophilic gel, composed of solid matrix and aqueous dispersion layer, similar to the two layer structure of tear film, that is, mucous layer and water layer, can adhere to the surface of the cornea, and form a liquid reservoir on the surface of the eyeball. Its polymer skeleton can release moisture after the action of electrolytes in the tear. The pharmacological property of Carbomer is to increase the viscosity of the matrix, so as to increase the adhesion and retention time of the preparation on the surface of the eyeball. Only ground contact is a thixotropic gel. Blinking can change its consistency. The water in the gel 1 times per blink can be partially released to replenish the tear. Therefore, it can effectively protect the sensitive cornea and conjunctival epithelium and prevent secondary symptoms of dry eye. There is no risk of application during pregnancy and lactation. It is suitable for alternative treatment of dry eye and reduced tear secretion.
3.5. Ganciclovir Gel
Ganciclovir is a 2 '- deoxy guanine nucleotide ANA-LOGue that inhibits herpes virus replication, and its ophthalmic gel is clinically used for herpes simplex keratitis.timolol maleate ophthalmic gel, 3.6., was prepared by using Carbomer as matrix and osmotic pressure regulator. The results showed that the effect of reducing intraocular pressure was significant and lasting. Once a day had the same effect as that of common eye drops of semaprolol maleate twice a day.
3.7. Compound Acyclovir Eye Gel
Compound acyclovir eye gel prepared by polyvinyl alcohol 124 and sodium carboxymethyl cellulose. The results of stability test and in vitro release test show that the preparation is stable in quality and has sustained release effect. It has no irritation to the eye and has a long duration.
3.8. Diphenylephrine Ophthalmic Gel
Wang liru and other preparations of diphenylephrine hydrochloride eye gel, dialysis membrane diffusion method for prescription in vitro release test, in vitro penetration test in vitro cornea. The results showed that the gel release in vitro accorded with the first-order release kinetics equation, and the corneal penetration behavior in vitro accorded with the first-order release law.
4. Application of Carbomer Gel in Other Fields
4.1. Hydrochlorothiazide Hydrophilic Gel Matrix Sustained-Release Tablets:
Hydrochlorothiazide is a powerful diuretic drug, it has low solubility in water, but has a high absorption rate in vivo and has good bioavailability. It is often used in combination with cardiovascular drugs in the treatment of essential hypertension, congestive heart failure and other cardiovascular diseases. Because the antihypertensive drugs need to be taken for a long time, in order to prevent the occurrence of adverse reactions, the development of the hydrophilic gel matrix sustained-release tablets can reduce the times of administration, increase the compliance of patients, maintain the stable state of blood concentration, avoid and reduce the fluctuation of blood concentration, so it is suitable for long-term application.
4.2. In Interventional Bronchoscopy
The treatment of multi drug resistant tuberculosis is a difficult problem in tuberculosis control at present. One of the main reasons is the hardening of the foci, the fibrosis of the foci and the destruction of the local blood vessels. It is difficult to form effective drug concentration locally after oral administration and intravenous application. Can not achieve the purpose of sterilization treatment. The chains of Carbomer polymer are covalently cross-linked to each other to form a network structure. When fully hydrated, it becomes a separate straight chain hydrated colloid structure, forming countless transmission channels. The drugs can diffuse evenly through this channel, maintain a high concentration of drugs in the local lesion for a long time, and play a role in killing mycobacterium tuberculosis.
4.3. Application in Oral Protein Polypeptide Drug Delivery System
Polypeptide oral drugs have always been prone to degradation and poor absorption and utilization. The key to solve this problem is to select appropriate enzyme inhibitors and absorption enhancers. It is found that Carbomer can inhibit the activity of some enzymes by complexing ca2 + and zn2 +, improve the permeability of cell membrane and promote the absorption of drugs. Moreover, it has 52% ~ 68% carboxyl groups in its own structure, which can release protons in the intestine to form local acidity and inhibit the activity of microbial protease, so Carbomer has great potential in polypeptide oral drug transport system.
4.4. In Gel Preparation of Traditional Chinese Medicine
Gel preparations of traditional chinese medicine are commonly used for skin or mucous membrane administration. At present, they are commonly used in dispelling stasis, easing pain, activating blood circulation, clearing heat, drying dampness, purging fire, detoxifying and scabies. Chinese herbal medicine contains more water soluble components and is suitable for hydrogel matrix. Xia hongde chose Carbomer as a substrate and extracted from chinese medicine such as radix scutellariae and rhubarb to prepare double yellow gel for herpes zoster. The hydrophilic gel of salvia miltiorrhiza was prepared by using the Carbomer as matrix, and the release in vitro was studied. It was found that the release of liposoluble drugs could be controlled by adjusting the hydrophilic and lipophilic ratio of the gel matrix.
5. Conclusion
Although most of the pharmaceutical preparations made with Carbomer as excipients are still in the experimental stage and only a few varieties are on the market, with the continuous deepening of the application of Carbomer in the pharmaceutical field, as a new polymer material with development potential and excellent pharmaceutical excipients, it will promote the research and development of more new pharmaceutical preparations.
